Dose distributions of the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care

Date of Approval
Application Number
21_000503
Technical Summary

Rationale: Therapeutic inertia, defined as “failure to advance therapy or to de-intensify therapy when appropriate to do so” is a well described phenomenon in T2DM. Failure to up-titrate therapies to optimal therapeutic doses in a timely manner is a component of therapeutic inertia, which has not been well studied in relation to GLP-1 RAs.

Aim: To determine the dose distributions of T2DM patients on dulaglutide or s.c. semaglutide to evaluate how well dosing in clinical practice follows recommendations and understand the proportion not on an optimal therapeutic dose.

Objectives: To describe the: i) dose distributions of dulaglutide and s.c. semaglutide at 3, 6, 9 and 12 months after first prescription, by patient and disease characteristics, ii) proportion of patients that escalate/de-escalate dosage of dulaglutide and s.c. semaglutide iii) proportion of patients achieving target HbA1c levels at each dose iv) dosages of the first prescriptions of dulaglutide and s.c. semaglutide v) BMI of patient at each dose .

Primary exposures: T2DM (diagnosis or prescription of 2+ classes of glucose lowering medication), and dulaglutide or s.c. semaglutide prescription within primary care.

Outcomes: dulaglutide/s.c. semaglutide dose distributions and alterations, target HbA1c achieved

Methods: A retrospective cohort study design using data from the CPRD GOLD primary care database to identify T2DM patients with a first prescription of dulaglutide or s.c. semaglutide in primary care (index date) between Jan-2019 and Jul-2019. Dose distribution will be described at 3, 6, 9 and 12 months following indexing, with follow-up extending up to March 2020. The proportions of patients achieving target HbA1c levels and in BMI categories will also be described at 3-6, 6-9 and 9-12 months following indexing.

Data analysis: Frequencies and percentages will be reported for categorical variables, while counts, means, medians, standard deviations (SDs), interquartile range, and minimum/maximum values will be reported for numeric variables.

Health Outcomes to be Measured

The starting dose, and subsequent dose escalations / de-escalations of dulaglutide or s.c. semaglutide; the number of concomitant T2DM medications taken at index; HbA1c levels during follow-up; BMI during follow-up

Collaborators

Jonathan Rachman - Chief Investigator - Eli Lilly & Co - UK
Robert Wood - Corresponding Applicant - Adelphi Real World
Amisha Patel - Collaborator - Adelphi Real World
Caroline Casey - Collaborator - Adelphi Real World
Christina Diomatari - Collaborator - Adelphi Real World
Iskandar Idris - Collaborator - University of Nottingham
Joanne Webb - Collaborator - Eli Lilly & Co Ltd - US Headquarters
Lill-Brith von Arx - Collaborator - Eli Lilly & Co - UK